Hematopoietic stem cell transplantation (HCT) has the potential to cure people with cancer and other life- threatening diseases. However, patients risk prolonged vulnerability to infections and other complications as well as substantial treatment-related mortality. Consequently, HCT typically occurs in the hospital, with stays lasting three months or more. Yet hospitalization is not without problems, including nosocomial infections, disrupted homeostasis, and increased resource utilization and costs. Patient-centered home transplant (PCHT) is a novel alternative that may improve patient safety, clinical efficacy, and value for HCT patients. PCHT begins with a comprehensive assessment of each patient's needs. This includes meetings with patients, caregivers, social workers, nutritionists, nurses, and physicians. Following an individualized care plan, clinicians visit patients in their homes every morning to perform assessments and draw labs. Labs are analyzed at the hospital, and nurses return to patient homes to deliver needed medical interventions (e.g. antibiotics, blood transfusions). Leveraging the power of our electronic health record, clinician laptops allow remote access to all of a patient's health information, potential drug interactions, and other important details. In addition, patients are provided with iPads to videoconference daily with physicians to report complications or concerns. We have successfully piloted this approach with HCT patients, demonstrating feasibility. By allowing patients to stay at home, PCHT may reduce exposure to hospital pathogens, decreasing nosocomial infections. PCHT may also reduce graft-versus-host disease (GVHD), which affects 40-60% of HCT patients and is a leading cause of morbidity and mortality. GVHD is driven by inflammation, which may be triggered by changes in the bacteria living in the gut. This gut microbiota is affected by changes in the environment (e.g. hospitalization); however, if patients stay in their normal environment (home), they may preserve their normal gut microbiota, decreasing inflammation and GVHD. Staying at home also may promote independence and improve quality of life (QOL) by allowing greater access to nutrition, exercise, and social support. While more intensive staffing may be needed, these advantages may combine to lower overall costs. This proposal describes a randomized phase 2 study to compare PCHT vs. standard care. The first aim is to compare clinical outcomes, include GVHD (primary endpoint), infections, survival, quality of life, and symptoms. Potential mediators of these outcomes (e.g. nutrition, exercise, social support, self -efficacy) will also be evaluated. The second aim is to evaluate the safety of this approach, assessing treatment-related mortality and adverse events. The third aim is to conduct an economic evaluation of the direct medical costs, health resources utilization, and indirect costs (e.g., patient time) with PCHT vs. standard care. The long-term objectives are to improve patient safety and longevity by preventing complications such as GVHD and infections, promote QOL, and lower costs while improving quality of care.